<i>Lamp1</i> Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in <i>Drosophila</i> Models of Parkinson Disease

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dc.contributor.authorRahmani, Zohra
dc.contributor.authorSurabhi, Satya
dc.contributor.authorRojo-Cortes, Francisca
dc.contributor.authorDulac, Amina
dc.contributor.authorJenny, Andreas
dc.contributor.authorBirman, Serge
dc.date.accessioned2025-01-20T21:01:30Z
dc.date.available2025-01-20T21:01:30Z
dc.date.issued2022
dc.description.abstractParkinson disease (PD) is a common neurodegenerative condition affecting people predominantly at old age that is characterized by a progressive loss of midbrain dopaminergic neurons and by the accumulation of alpha-synuclein-containing intraneuronal inclusions known as Lewy bodies. Defects in cellular degradation processes such as the autophagy-lysosomal pathway are suspected to be involved in PD progression. The mammalian Lysosomal-associated membrane proteins LAMP1 and LAMP2 are transmembrane glycoproteins localized in lysosomes and late endosomes that are involved in autophagosome/lysosome maturation and function. Here, we show that the lack of Drosophila Lamp1, the homolog of LAMP1 and LAMP2, severely increased fly susceptibility to paraquat, a pro-oxidant compound known as a potential PD inducer in humans. Moreover, the loss of Lamp1 also exacerbated the progressive locomotor defects induced by the expression of PD-associated mutant alpha-synuclein A30P (alpha-synA30P) in dopaminergic neurons. Remarkably, the ubiquitous re-expression of Lamp1 in a mutant context fully suppressed all these defects and conferred significant resistance towards both PD factors above that of wild-type flies. Immunostaining analysis showed that the brain levels of alpha-synA30P were unexpectedly decreased in young adult Lamp1-deficient flies expressing this protein in comparison to non-mutant controls. This suggests that Lamp1 could neutralize alpha-synuclein toxicity by promoting the formation of non-pathogenic aggregates in neurons. Overall, our findings reveal a novel role for Drosophila Lamp1 in protecting against oxidative stress and alpha-synuclein neurotoxicity in PD models, thus furthering our understanding of the function of its mammalian homologs.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms232113078
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://doi.org/10.3390/ijms232113078
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92899
dc.identifier.wosidWOS:000881304600001
dc.issue.numero21
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectLamp1
dc.subjectalpha-synuclein
dc.subjectparaquat
dc.subjectParkinson disease
dc.subjectDrosophila
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.title<i>Lamp1</i> Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in <i>Drosophila</i> Models of Parkinson Disease
dc.typeartículo
dc.volumen23
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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